Dataset Information

Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.

ABSTRACT: The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4707064 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.

Zhang Ye Y Sloan Steven A SA Clarke Laura E LE Caneda Christine C Plaza Colton A CA Blumenthal Paul D PD Vogel Hannes H Steinberg Gary K GK Edwards Michael S B MS Li Gordon G Duncan John A JA Cheshier Samuel H SH Shuer Lawrence M LM Chang Edward F EF Grant Gerald A GA Gephart Melanie G Hayden MG Barres Ben A BA

Neuron 20151210 1

The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to ...[more]

PMID: 26687838

Similar Datasets

Project description:BACKGROUND:The two Caenorhabditis elegans somatic gonadal precursors (SGPs) are multipotent progenitors that generate all somatic tissues of the adult reproductive system. The sister cells of the SGPs are two head mesodermal cells (hmcs); one hmc dies by programmed cell death and the other terminally differentiates. Thus, a single cell division gives rise to one multipotent progenitor and one differentiated cell with identical lineage histories. We compared the transcriptomes of SGPs and hmcs in order to learn the determinants of multipotency and differentiation in this lineage. RESULTS:We generated a strain that expressed fluorescent markers specifically in SGPs (ehn-3A::tdTomato) and hmcs (bgal-1::GFP). We dissociated cells from animals after the SGP/hmc cell division, but before the SGPs had further divided, and subjected the dissociated cells to fluorescence-activated cell sorting to collect isolated SGPs and hmcs. We analyzed the transcriptomes of these cells and found that 5912 transcripts were significantly differentially expressed, with at least two-fold change in expression, between the two cell types. The hmc-biased genes were enriched with those that are characteristic of neurons. The SGP-biased genes were enriched with those indicative of cell proliferation and development. We assessed the validity of our differentially expressed genes by examining existing reporters for five of the 10 genes with the most significantly biased expression in SGPs and found that two showed expression in SGPs. For one reporter that did not show expression in SGPs, we generated a GFP knock-in using CRISPR/Cas9. This reporter, in the native genomic context, was expressed in SGPs. CONCLUSIONS:We found that the transcriptional profiles of SGPs and hmcs are strikingly different. The hmc-biased genes are enriched with those that encode synaptic transmission machinery, which strongly suggests that it has neuron-like signaling properties. In contrast, the SGP-biased genes are enriched with genes that encode factors involved in transcription and translation, as would be expected from a cell preparing to undergo proliferative divisions. Mediators of multipotency are likely to be among the genes differentially expressed in SGPs.

Dataset Information

Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.

Publications

Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets